Periodontal diseases are a major problem in the human dentition. In fact, more teeth are lost from periodontal disease than from dental caries. Thus, there is a great need for reliable diagnostic tests for periodontal disease; in particular there is a need for early stage diagnosis of the onset of the disease, even in early gingivitis stage i.e. diagnosis of the early stages of beginning tissue destruction before visible signs of the destruction have occurred.
Periodontal disease comprises a group of inflammatory disorders originating from infections affecting the gingiva (gum) and the alveolar jaw bone structures supporting the teeth.
The primary cause of periodontal diseases is bacterial plaque and bacterial biofilm attached to the teeth. They cause inflammation of the gum which may result in destruction of the actual tooth-supporting structures and bone in periodontal disease. There is usually a large accumulation of bacteria in plaque and biofilm, both above (supragingival) and below (subgingival) the gum line.
Gingivitis (gum inflammation) is distinguished from periodontitis in that in gingivitis, gingiva are inflamed but no deep (>4 mm) periodontal pockets are detectable; thus, no irreversible destruction of soft and hard (bony) tooth supporting structures is associated with gingivitis. Periodontitis is characterized by inflamed gingiva and destruction of soft and hard (bony) tooth supporting structures; however, periodontitis can be missed in clinically-healthy-looking gingiva.
Even though vast research and development in improved diagnostic systems has been performed in the past 20 years reflected in an increase in publications (e.g. Pubmed search April 2010/July 2013: MMP-8 640/891 Citations, MMP-8 in Periodont-/Implantology 95/136 Citations) periodontal disease and its successor in dental implants peri-implantitis still causes billions in dental treatment costs.
In spite of an increasing awareness, major efforts in treatment and meanwhile the availability of improved test systems that are able to identify the disease chair side or by means of lab testing, the disease is spreading/growing dramatically (Deutsche Mund Gesundheits Studie IV, 2006) in industrialized countries e.g. Germany.
“According to the CDC definition considering mesiobuccal and distolingual sites, prevalence of periodontitis was 70.9% and 87.4% in both age cohorts, with one-fourth and one-half presenting severe forms, respectively.” (B. Holtfreter et al., 2010)
In the past 25 years, a dramatic progress has been made in restorative technologies by the development of dental implants that can replace teeth, which have gone lost by periodontitis and other causes in the years before.
However the same or a similar pathology applies for dental implants, as it does for natural teeth in periodontitis.
As described above for natural teeth, periodontitis is mainly caused by pathogens in biofilm that adheres to the implant surface, to and in the connection between an implant and the abutment and to the prosthetic supra construction a similar host reaction of tissue surrounding the dental implant is provoked: triggered by bacterial debris (LPS), an inflammatory reaction is induced that may get out of control and in its course will discharge high amounts of proteases, mainly MMP-8.
Similar to natural teeth, an unbalanced activation of MMP-8 may lead to hyperactivation and extremely high concentrations of active MMP-8 (aMMP-8) in peri-implant sulcus fluid (PISF) (Ma J, et al., 2000, Xu L et al., 2008) and may within an individually unpredictable time lead to a significant loss of alveolar bone (peri-implantitis) and in consequence to a loss of the implant.
Once in a stage of peri-implantitis there are little options for treating the disease. Equivalent to periodontitis in peri-implantitis clinical diagnosis (Ma J, et al.: 2000 and Xu L, et al. 2008) means measurement of the level of destruction the disease has already caused e.g. by probing of attachment loss or inspection of an x-ray. Other methods like analysing proteins, have proven not to be specific enough or the parameters are not accessible by means of chair-side diagnostics or the relevant biological samples are not stable to be sent to an specialized laboratory for routine diagnosis.
Therefore it is still of major interest for dental professionals, for medical professionals and even for the patient's home monitoring, to develop test systems, especially rapid chair side tests, that are capable to recognize not only active proteases (such as MMP-8) but already the activation process. This may allow for an improved predictive judgement or prognostic analysis of the individual periodontal situation, which is important in case of an upcoming or existing periodontal disease at natural dentition and in case of implants for early detection of the risk for peri-implant disorders.
It will enable medical doctors to refer risk patients to dental professional as early as possible, and it will enable dental professionals to apply an earlier preventive treatment and it will motivate patients to exert better oral hygiene. Early detection and subsequent prophylactic treatment of periodontal disease/disorders may—as health care systems have learned before in caries prophylaxis—help save billions of treatment and restorative cost.
Moreover, today it is well documented, that (chronic) periodontitis is interacting with numerous systemic diseases and is regarded to be a significant risk factor in numerous systemic diseases such as diabetes, myocard infarction (MI), stroke and other cardiovascular and neurological diseases (CVD), chronic obstructive pulmonary disease (COPD), rheumatoid arthritis (RA), morbus Crohn (MC), sepsis, HIV, borreliosis and other systemic low grade inflammations, metabolic syndrome, obesity, nephropathies, tissue transplantation, orthopaedic disorders and for pre-term delivery (PTD), low birth weight and reproductive risks such as erectile dysfunction, reduced sperm count and lower mobility of the sperm cells.
For example the odds ratios increase for patients with periodontitis versus periodontally healthy patients with diabetes (death rate)=7.7, for PTD 7.5, for stroke=8.5. Periodontitis is a well-recognized risk factor for MI, diabetes and stroke. Many of these studies have also shown the relevance of MMP-8 as a systemic and local (oral) biomarker of the periodontal disease.
As such the capability to diagnose the early onset of periodontal disease and to identify those patients at risk of developing or progressing periodontal disorders with prognostic test systems is crucial not only within the dental industry/field but in fact to the entire medical industry/field and the health care system. AETNA, an US health care insurance has proven that over all heath cost of e.g. diabetics that have undergone periodontal treatment versus those without periodontal treatment was reduced by 16%, indicating the significance and impact of oral diseases and giving reason to think about what an improved early detection of periodontal risks in combination with prophylactic treatment may mean for patients and total health care cost in the future.
Systemical MMP-8 also plays a role in other diseases. The predominant role of MMP-8 in extracellular matrix turnover, modulation of inflammatory responses and other physiological processes, the involvement of MMP-8 in a wide range of pathologies and the role of MMP-8 as a drug target or disease marker in some inflammatory disorders and in cancer progression is well documented. MMP-8 is described as a possible drug target in a wide range of inflammatory disorders and in patients, elevated MMP-8 levels are often associated with progression of inflammatory disease (Dejonckheere E. et al., 2011).
It has been found that early high serum MMP-8 levels predict fatal outcome in septic infections and in cardiovascular diseases. Further, it has been shown that patients with bacterial meningitis (BM) have high or elevated MMP-8 levels in cerebrospinal fluid (CSF) and also that the MMP-8 levels in CSF of children with BM are significantly higher among non-survivors than among survivors.
It is also known that inflammation and/or infection in amniotic fluid is a risk factor for preterm birth and adverse neonatal outcome. MMP-8 has been used as a marker for prediction and diagnosis of infection/inflammation and also for the development of preterm birth and neonatal complications.